1. Technical Field
The present invention is related to anti-inflammatory compounds. More particularly, the present invention is related to a new family of synthetic peptides having potent anti-inflammatory activity and a method for controlling or alleviating inflammation.
2. State Of The Art
Inflammatory reactions are involved in a large number of human diseases. Some steroid hormones are well known modulators of inflammation. It has been suggested that the steroids exert their effect by decreasing the level of tissue prostanoids which are known mediators of inflammatory reactions (for review, see Ferreira, Handbook of Inflammatory Diseases 5:107-116, 1985). One of the key enzymes controlling the level of arachidonic acid, the substrate for prostaglandin synthesis, is phospholipase A.sub.2. A possible mechanism for preventing inflammation is the inhibition of this enzyme, thereby lowering the level of tissue prostanoids (Flower et al, Nature 278:456-459, 1979; Russo-Marie et al, Biochem. Biophys. Acta. 712:177-185, 1982; and Hirata Advances in Prostaglandin, Thromoxane and Leukotriene Research 2:73-78, 1983).
During the past decade several corticosteroid dependent low molecular weight proteins with phospholipase A.sub.2 (PLA.sub.2) inhibitory activity have been described (Hirata et al, Biochem, Biophys. Res. 109:223-230, 1982). Lipocortins (DiRosa et al, Prostaglandins 28:441-443, 1984), a family of such inhibitors induced by corticosteroids, are suggested to be the mediators of anti-inflammatory action of these steroids. A genetically different protein, blastokinin, also known as uteroglobin, is a potent PLA.sub.2 inhibitor (Levin et al, Life Sci. 38:1813-1819, 1986). Heretofore, however, small peptides that consist of 15 or fewer amino acid residues, which include VLDS as a preferred, but not necessarily essential, portion thereof, and that possess potent PLA.sub.2 inhibitory and anti-inflammatory activity, such as the antiflammin peptides of this invention, have not been known or described.